Submissions for variant NM_001353345.2(SETD1B):c.5530A>G (p.Met1844Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003235831	SCV003932907	uncertain significance	not provided	2023-12-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004587479	SCV005076150	uncertain significance	not specified	2024-04-15	criteria provided, single submitter	clinical testing	Variant summary: SETD1B c.5530A>G (p.Met1844Val) results in a conservative amino acid change located in the SET domain (IPR001214) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 166074 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5530A>G in individuals affected with Intellectual Developmental Disorder With Seizures And Language Delay and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2505599). Based on the evidence outlined above, the variant was classified as uncertain significance.