ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.260C>T (p.Pro87Leu) (rs144900708)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036563 SCV000060218 uncertain significance not specified 2012-10-03 criteria provided, single submitter clinical testing The Pro77Leu variant in TNNT2 has been identified in 1 individual with HCM/SCD ( Varnava 2001) as well as in 1/8600 European American chromosomes from a broad po pulation by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS /; dbSNP rs144900708). Proline (Pro) at position 77 is conserved in mammals and some evolutionarily distant species, but frog and stickleback carry a leucine (L eu; this variant) at this position suggesting that this change may be tolerated. Other computational analyses (biochemical amino acid properties, AlignGVGD, Pol yPhen2, and SIFT) suggest that this variant may not impact the protein, though t his information is not predictive enough to rule out pathogenicity. Additional s tudies are needed to fully assess the clinical significance of this variant.
Invitae RCV000646057 SCV000767814 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 77 of the TNNT2 protein (p.Pro77Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs144900708, ExAC 0.02%). This variant has been reported in individuals affected with hypertrophic cardiomyopathy (HCM), including a mother with HCM and her son with left-ventricular-non-compaction (LVNC) (PMID: 11560853, 20530761). This variant is also known as p.Pro87Leu in the literature. ClinVar contains an entry for this variant (Variation ID: 43619). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
CSER_CC_NCGL; University of Washington Medical Center RCV000148902 SCV000190648 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research

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