Submissions for variant NM_001375808.2(LPIN2):c.1720T>A (p.Ser574Thr)

gnomAD frequency: 0.00001  dbSNP: rs148779863

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414093	SCV000492426	uncertain significance	not specified	2016-12-13	criteria provided, single submitter	clinical testing	The S574T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, S574T is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001861440	SCV002167909	uncertain significance	Majeed syndrome	2022-08-21	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 574 of the LPIN2 protein (p.Ser574Thr). This variant is present in population databases (rs148779863, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with LPIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373803). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263667	SCV002543536	uncertain significance	Autoinflammatory syndrome	2021-04-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002521444	SCV003625465	uncertain significance	Inborn genetic diseases	2022-05-11	criteria provided, single submitter	clinical testing	The c.1720T>A (p.S574T) alteration is located in exon 13 (coding exon 12) of the LPIN2 gene. This alteration results from a T to A substitution at nucleotide position 1720, causing the serine (S) at amino acid position 574 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.